During the first three years of this project we have performed a systematic quantitative investigation of image quality and vessel visibility as a function of imaging parameters for multiple overlapping thin slab acquisition (MOTSA) including the optimization of gradient waveforms in an attempt to achieve the highest possible spatial resolution and visualization of the smallest possible vessel detail. Our goal has been to improve the MOTSA technique to the point where intracranial arterial vessels on the order of 0.3 to 0.5 mm in diameter will be routinely visualized throughout a diagnostically useful region in a reasonable examination time. In pursuit of this goal we have developed unique tools for the measurement of vessel contrast-to-noise ratio (CNR) and receiver-operating-characteristic (ROC) analysis for vessel visibility and we have performed a systematic study of vessel visibility as a function of flow geometries and imaging parameters. While this detailed analysis has documented situations in which a significant improvement in vessel detail can be obtained, the study has also (1) pointed to other fundamental properties which can be modified to further improve the visibility of small vessels and (2) suggested further potential causes for the loss in small-vessel detail. In this process we developed a better understanding of those factors which continue to inhibit the visibility of small vessels in MOTSA MRA. The primary focus of this next funding period will be to perform a comprehensive evaluation of those factors which are predicted to further increase vessel visibility. These factors include improved RF coil and gradient waveform design, more efficient techniques of soft tissue suppression with a novel reduced power magnetization transfer (MT) sequence and the use of contrast agents. We will test some additional causes of loss in small-vessel detail including the effects of pulsatile brain motion by implementing cardiac-gated sequences. We will quantitate the extent to which each of these techniques will increase the visibility of small vessels in both normal controls and patients with proven intracranial vascular abnormalities. Finally, we will investigate the additional benefits of newly developed black-blood techniques using 3D fast spin echo (FSE). Our secondary focus during these next three years will be to maximize the tools developed above in visualization of common carotid bifurcation atherosclerosis. We will test if there are objective improvements in the quantification of lumen dimensions as compared to x-ray angiography. Finally we will use these tools to begin a pilot study of atherosclerotic plaque characterization including morphology and lipid composition. Successful completion of this project will lead to further understanding of the strengths and weaknesses of the proposed MRA and MRI techniques. In the near future this improved body of knowledge will be applied to prospective clinical trials to establish the efficacy and utility of these non-invasive techniques in diagnosing neurovascular disease in humans.